Association of a Polygenic Risk Score with Osteoporosis in People Living with HIV: The Swiss HIV Cohort Study

Abstract Background Bone mineral density (BMD) loss may be accelerated in people with HIV (PLWH). It is unknown whether an individual polygenic risk score (PRS) is associated with low BMD in PLWH. Methods We included Swiss HIV Cohort Study participants of self-reported European descent, each with >2 per-protocol Dual X-ray Absorptiometry (DXA) measurements >2 years apart (2011-2020). We obtained uni-/multivariable odds ratios (OR) for DXA-defined osteoporosis based on traditional and HIV-related osteoporosis risk factors and a genome-wide PRS built from 9413 single nucleotide polymorphisms associated with low BMD in the general population. Controls were free from osteoporosis/osteopenia on all DXA measurements. Results We included 438 participants (149 with osteoporosis, 289 controls; median age, 53 years, 82% male, 95% with suppressed HIV RNA). Participants with unfavorable osteoporosis-PRS (top vs. bottom PRS quintile) had univariable and multivariable-adjusted osteoporosis OR=4.76 (95% confidence interval [CI], 2.34-9.67) and 4.13 (1.86-9.18), respectively. For comparison, hepatitis C seropositivity, 5-year tenofovir disoproxil fumarate exposure, and parent history of hip fracture had univariable osteoporosis-OR=2.26 (1.37-3.74), 1.84 (1.40-2.43), and 1.54 (0.82-2.9), respectively. Conclusions In PLWH in Switzerland, osteoporosis was independently associated with a BMD-associated PRS, after adjustment for established osteoporosis risk factors including exposure to tenofovir DF.